PDBsum entry 2gcp

Signaling protein

PDB id: 2gcp

Contents

Protein chain

178 a.a. *

Ligands

GSP

EDO ×2

Metals

_MG ×3

Waters ×157

* Residue conservation analysis

PDB id:

2gcp

Name:

Signaling protein

Title:

Crystal structure of the human rhoc-gsp complex

Structure:

Rho-related gtp-binding protein rhoc. Chain: a. Synonym: rho cdna clone 9, h9. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: arh9, arhc, rhoc. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.15Å R-factor: 0.162 R-free: 0.226

Authors:

S.M.G.Dias,R.A.Cerione

Key ref:

S.M.Dias and R.A.Cerione (2007). X-ray crystal structures reveal two activated states for RhoC. Biochemistry, 46, 6547-6558. PubMed id: 17497936 DOI: 10.1021/bi700035p

Date:

14-Mar-06 Release date: 27-Mar-07

Protein chain

P08134  (RHOC_HUMAN) -  Rho-related GTP-binding protein RhoC from Homo sapiens

Seq: 193 a.a.

Struc: 178 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1021/bi700035p

Biochemistry 46:6547-6558 (2007)

PubMed id: 17497936

X-ray crystal structures reveal two activated states for RhoC.

S.M.Dias, R.A.Cerione.

ABSTRACT

RhoC is a member of the Rho family of Ras-related (small) GTPases and shares significant sequence similarity with the founding member of the family, RhoA. However, despite their similarity, RhoA and RhoC exhibit different binding preferences for effector proteins and give rise to distinct cellular outcomes, with RhoC being directly implicated in the invasiveness of cancer cells and the development of metastasis. While the structural analyses of the signaling-active and -inactive states of RhoA have been performed, thus far, the work on RhoC has been limited to an X-ray structure for its complex with the effector protein, mDia1 (for mammalian Diaphanous 1). Therefore, in order to gain insights into the molecular basis for RhoC activation, as well as clues regarding how it mediates distinct cellular responses relative to those induced by RhoA, we have undertaken a structural comparison of RhoC in its GDP-bound (signaling-inactive) state versus its GTP-bound (signaling-active) state as induced by the nonhydrolyzable GTP analogues, guanosine 5'-(beta,gamma-iminotriphosphate) (GppNHp) and guanosine 5'-(3-O-thiotriphosphate) (GTPgammaS). Interestingly, we find that GppNHp-bound RhoC only shows differences in its switch II domain, relative to GDP-bound RhoC, whereas GTPgammaS-bound RhoC exhibits differences in both its switch I and switch II domains. Given that each of the nonhydrolyzable GTP analogues is able to promote the binding of RhoC to effector proteins, these results suggest that RhoC can undergo at least two conformational transitions during its conversion from a signaling-inactive to a signaling-active state, similar to what has recently been proposed for the H-Ras and M-Ras proteins. In contrast, the available X-ray structures for RhoA suggest that it undergoes only a single conformational transition to a signaling-active state. These and other differences regarding the changes in the switch domains accompanying the activation of RhoA and RhoC provide plausible explanations for the functional specificity exhibited by the two GTPases.